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WO2008122789A3 - Methods for modulating lrrk2 - Google Patents

Methods for modulating lrrk2 Download PDF

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Publication number
WO2008122789A3
WO2008122789A3 PCT/GB2008/001211 GB2008001211W WO2008122789A3 WO 2008122789 A3 WO2008122789 A3 WO 2008122789A3 GB 2008001211 W GB2008001211 W GB 2008001211W WO 2008122789 A3 WO2008122789 A3 WO 2008122789A3
Authority
WO
WIPO (PCT)
Prior art keywords
lrrk2
compound
protein kinase
kinase activity
polypeptide
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/GB2008/001211
Other languages
French (fr)
Other versions
WO2008122789A2 (en
Inventor
Dario Alessi
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Medical Research Council
Original Assignee
Medical Research Council
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Medical Research Council filed Critical Medical Research Council
Priority to EP08718997A priority Critical patent/EP2132326B1/en
Priority to JP2010501595A priority patent/JP2010523101A/en
Priority to CA2718580A priority patent/CA2718580A1/en
Priority to CN200880017563A priority patent/CN101688234A/en
Priority to DK08718997.3T priority patent/DK2132326T3/en
Priority to US12/244,715 priority patent/US7947468B2/en
Publication of WO2008122789A2 publication Critical patent/WO2008122789A2/en
Publication of WO2008122789A3 publication Critical patent/WO2008122789A3/en
Priority to US12/553,932 priority patent/US8206942B2/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/48—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving transferase
    • C12Q1/485—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving transferase involving kinase
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A61P25/16—Anti-Parkinson drugs
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Genetics & Genomics (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Animal Behavior & Ethology (AREA)
  • Physics & Mathematics (AREA)
  • Analytical Chemistry (AREA)
  • Biophysics (AREA)
  • Medicinal Chemistry (AREA)
  • Biotechnology (AREA)
  • Immunology (AREA)
  • Microbiology (AREA)
  • Molecular Biology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Biochemistry (AREA)
  • General Engineering & Computer Science (AREA)
  • Psychology (AREA)
  • Enzymes And Modification Thereof (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Investigating Or Analysing Biological Materials (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)

Abstract

A method for identifying a compound expected to be useful in modulating a LRRK2 protein kinase activity, the method comprising the steps of (1) determining whether a test compound modulates the protein kinase activity of a LRRK2 polypeptide on a substrate Ezrin/Radixin/moesin (ERM) family polypeptide and (2) selecting a compound which modulates the LRRK2 polypeptide protein kinase activity. Such a compound may be useful in treating Parkinson's Disease or Parkinsonism. A catalytically active fragment of LRRK2 is identified, requiring the GTPase, COR and kinase domains as well as the WD_40-like motif and C-terminal tail.
PCT/GB2008/001211 2007-04-05 2008-04-07 Methods for modulating lrrk2 Ceased WO2008122789A2 (en)

Priority Applications (7)

Application Number Priority Date Filing Date Title
EP08718997A EP2132326B1 (en) 2007-04-05 2008-04-07 Methods
JP2010501595A JP2010523101A (en) 2007-04-05 2008-04-07 Adjustment method of LRRK2
CA2718580A CA2718580A1 (en) 2007-04-05 2008-04-07 Methods for identifying kinase modulators
CN200880017563A CN101688234A (en) 2007-04-05 2008-04-07 Method of modulating LRRK2
DK08718997.3T DK2132326T3 (en) 2007-04-05 2008-04-07 APPROACHES
US12/244,715 US7947468B2 (en) 2007-04-05 2008-10-02 Methods
US12/553,932 US8206942B2 (en) 2007-04-05 2009-09-03 Methods of identifying LRRK2 inhibitors

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US91024207P 2007-04-05 2007-04-05
GBGB0706709.3A GB0706709D0 (en) 2007-04-05 2007-04-05 Methods
GB0706709.3 2007-04-05
US60/910,242 2007-04-05

Related Child Applications (2)

Application Number Title Priority Date Filing Date
US12/244,715 Continuation-In-Part US7947468B2 (en) 2007-04-05 2008-10-02 Methods
PCT/GB2009/002047 Continuation-In-Part WO2010031988A2 (en) 2007-04-05 2009-08-24 Methods

Publications (2)

Publication Number Publication Date
WO2008122789A2 WO2008122789A2 (en) 2008-10-16
WO2008122789A3 true WO2008122789A3 (en) 2008-12-04

Family

ID=38090954

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/GB2008/001211 Ceased WO2008122789A2 (en) 2007-04-05 2008-04-07 Methods for modulating lrrk2

Country Status (8)

Country Link
US (1) US7947468B2 (en)
EP (1) EP2132326B1 (en)
JP (1) JP2010523101A (en)
CN (1) CN101688234A (en)
CA (1) CA2718580A1 (en)
DK (1) DK2132326T3 (en)
GB (1) GB0706709D0 (en)
WO (1) WO2008122789A2 (en)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9156845B2 (en) 2012-06-29 2015-10-13 Pfizer Inc. 4-(substituted amino)-7H-pyrrolo[2,3-d] pyrimidines as LRRK2 inhibitors
CN108709997B (en) * 2018-05-28 2020-09-18 中国林业科学研究院林业研究所 Substrate search method for LRR receptor kinase

Families Citing this family (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB0706709D0 (en) 2007-04-05 2007-05-16 Medical Res Council Methods
US8206942B2 (en) 2007-04-05 2012-06-26 Medical Research Council Methods of identifying LRRK2 inhibitors
GB2463656B (en) * 2008-09-18 2010-10-13 Medical Res Council Substrate of LRRK2 and methods of assessing LRRK2 activity
JP2012254937A (en) * 2009-09-11 2012-12-27 Kyushu Univ New matrix peptide of rho-kinase
WO2011036211A1 (en) * 2009-09-23 2011-03-31 Institut National De La Sante Et De La Recherche Medicale (Inserm) Polypeptides and nucleic acids for treating erbb2-dependent cancers
US8367349B2 (en) * 2010-04-19 2013-02-05 Medical Research Council Methods for identifying modulators of LRRK2
KR101687060B1 (en) * 2010-10-08 2016-12-15 상하이 켁신 바이오테크 씨오., 엘티디. Moesin modulators and uses thereof
JP5696220B2 (en) * 2010-10-08 2015-04-08 シャンハイ クーシン バイオテック カンパニー，リミテッド Method and kit for diagnosing immune thrombocytopenia, and use of moesin fragment in the manufacture of diagnostic compositions
WO2012045273A1 (en) 2010-10-08 2012-04-12 Shanghai Kexin Biotech Co., Ltd. Moesin fragments and uses thereof
CA2814026C (en) * 2010-10-08 2017-07-11 Shanghai Kexin Biotech Co., Ltd. Moesin fragments associated with aplastic anemia
US9345765B2 (en) 2010-10-08 2016-05-24 Shanghai Kexin Biotech Co., Ltd. Diagnostic and therapeutic uses of moesin fragments
MX2013005801A (en) * 2010-11-30 2013-07-17 Genentech Inc Assays and biomarkers for lrrk2.
ES2663622T3 (en) 2013-12-17 2018-04-16 Pfizer Inc. Novel 1-pyrrolo [2,3-b] 3,4-disubstituted pyridines and 7H-4,5-disubstituted pyridacins [2,3-c] pyridazines as inhibitors of LRRK2
WO2015176010A1 (en) 2014-05-15 2015-11-19 The United States Of America, As Represented By The Secretary, Departmentof Health & Human Services Treatment or prevention of an intestinal disease or disorder
MX377305B (en) 2015-09-14 2025-03-07 Pfizer NOVEL IMIDAZO[4,5-c]QUINOLINE AND IMIDAZO[4,5-c][1,5]NAPHTHYRIDINE DERIVATIVES AS LRRK2 INHIBITORS.
US20180179594A1 (en) * 2016-10-31 2018-06-28 Parkinson's Institute Multiple system atrophy and the treatment thereof
CN112843067B (en) * 2019-11-26 2023-01-06 兰州大学 Human LRRK2 protein small-molecule inhibitor and application thereof

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20030166222A1 (en) * 2002-01-02 2003-09-04 Millennium Pharmaceuticals, Inc. 39267, human kinase family members and uses therefor
WO2004074485A1 (en) * 2003-02-24 2004-09-02 Research Association For Biotechnology Novel proteins and dnas encoding the same
US20040265849A1 (en) * 2002-11-22 2004-12-30 Applera Corporation Genetic polymorphisms associated with Alzheimer's disease, methods of detection and uses thereof

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ATE431426T1 (en) 2006-03-14 2009-05-15 Cellzome Ag METHOD FOR IDENTIFYING LRRK2 INTERACTING MOLECULES AND FOR PURIFYING LRRK2
WO2008091799A2 (en) 2007-01-22 2008-07-31 The Trustees Of Columbia University In The City Of New York Cell-based methods for identifying inhibitors of parkinson's disease-associated lrrk2 mutants
GB0706709D0 (en) 2007-04-05 2007-05-16 Medical Res Council Methods

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20030166222A1 (en) * 2002-01-02 2003-09-04 Millennium Pharmaceuticals, Inc. 39267, human kinase family members and uses therefor
US20040265849A1 (en) * 2002-11-22 2004-12-30 Applera Corporation Genetic polymorphisms associated with Alzheimer's disease, methods of detection and uses thereof
WO2004074485A1 (en) * 2003-02-24 2004-09-02 Research Association For Biotechnology Novel proteins and dnas encoding the same

Non-Patent Citations (5)

* Cited by examiner, † Cited by third party
Title
DATABASE UniProt [online] 11 October 2005 (2005-10-11), "SubName: Full=Putative uncharacterized protein; Flags: Fragment;", XP002494863, retrieved from EBI accession no. UNIPROT:Q3UF33 Database accession no. Q3UF33 *
JALEEL MAHABOOBI ET AL: "LRRK2 phosphorylates moesin at threonine-558: characterization of how Parkinson's disease mutants affect kinase activity", BIOCHEMICAL JOURNAL, vol. 405, no. Part 2, July 2007 (2007-07-01), pages 307 - 317, XP002494862, ISSN: 0264-6021(print) 1470-8728(ele *
KATAYAMA S ET AL: "Antisense transcription in the mammalian transcriptome", SCIENCE, AMERICAN ASSOCIATION FOR THE ADVANCEMENT OF SCIENCE, US, WASHINGTON, DC, vol. 309, no. 5740, 2 September 2005 (2005-09-02), pages 1564 - 1566, XP003020135, ISSN: 0036-8075 *
MATA ET AL: "LRRK2 in Parkinson's disease: protein domains and functional insights", TRENDS IN NEUROSCIENCE, ELSEVIER, AMSTERDAM, NL, vol. 29, no. 5, 1 May 2006 (2006-05-01), pages 286 - 293, XP005415125, ISSN: 0166-2236 *
MATSUI T ET AL: "RHO-KINASE PHOSPHORYLATES COOH-TERMINAL THREONINES OF EZRIN/RADIXIN/MOESIN (ERM) PROTEINS AND REGULATES THEIR HEAD-TO-TAIL ASSOCIATION", THE JOURNAL OF CELL BIOLOGY, ROCKEFELLER UNIVERSITY PRESS, US, vol. 140, no. 3, 9 February 1998 (1998-02-09), pages 647 - 657, XP001083757, ISSN: 0021-9525 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9156845B2 (en) 2012-06-29 2015-10-13 Pfizer Inc. 4-(substituted amino)-7H-pyrrolo[2,3-d] pyrimidines as LRRK2 inhibitors
CN108709997B (en) * 2018-05-28 2020-09-18 中国林业科学研究院林业研究所 Substrate search method for LRR receptor kinase

Also Published As

Publication number Publication date
CN101688234A (en) 2010-03-31
US20090142784A1 (en) 2009-06-04
CA2718580A1 (en) 2008-10-16
JP2010523101A (en) 2010-07-15
US7947468B2 (en) 2011-05-24
DK2132326T3 (en) 2012-12-17
WO2008122789A2 (en) 2008-10-16
EP2132326A2 (en) 2009-12-16
GB0706709D0 (en) 2007-05-16
EP2132326B1 (en) 2012-10-31

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